Neurons from blood-derived stem cells as a model of A-T neurodegeneration.

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Ron Hart

Research Project Information

Principal Researchers: Professor Ron Hart
Institute: University of Rutgers, United States of America
Project Completion Date: April 2015

 Project Overview

Ataxia Telangiectasia (A-T) is caused by defects in the ATM (Ataxia Telangiectasia Mutated) gene and the associated ATM protein. Similar to other neurodegenerative conditions, such as Alzheimer’s and Parkinson’s disease, some of the most devastating symptoms of A-T are due to the death of neurons (nerve cells) within the brain. Professor Hart and his research team’s past work has focused on studying how the ATM gene affected in A-T causes this neurodegeneration. For such studies, human neurons are desirable.

Stem cells have the remarkable potential to develop into many different types of cell, including neurons. The main goal of this project was to prepare stem cells from the blood samples of A-T patients and make these cells readily available to the scientific community for future A-T studies.

Project Outcome

Professor Hart and his research team collected blood samples from 5 A-T patients and 10 clinically unaffected carriers of the defective ATM gene. The team successfully prepared stem cells from two of the unaffected carriers. One A-T stem cell line was successfully prepared. Unfortunately, an attempt to make a second A-T stem cell line failed due to technical difficulties.

Publications

The following articles have been published since the grant end date.

  • Lin, L., M.R. Swerdel, M.P. Lazaropoulos, G.S. Hoffman, A.J. Toro-Ramos, J. Wright, H.Lederman, J. Chen, J.C. Moore and R.P. Hart. Spontaneous ATM gene reversion in A-T iPSC to produce an isogenic cell line. Stem Cell Reports, 2015, 5, 1097-1108
  • Jiang, D., Y. Zhang, R.P. Hart, J. Chen, K. Herrup and J. Li. Alteration in 5-hydroxymethylcytosine-mediated epigenetic regulation leads to Purkinje cell vulnerability in ATM-deficiency. Brain, 2015, 138, 3520-3536

What next?

The stem cells prepared provide promising opportunities for identifying the cause of A-T symptoms and potential drug treatments for patients. This high value has led to the A-T Children’s Project providing a further 12 months of financial support, to enable completion of the project. Future work by the research team will focus on preparing more stem cell lines (with different ATM gene defects) and establishing methods for assessing the functioning of the faulty ATM gene within these cells.